title: Towards translation of 212Pb as a clinical therapeutic; getting the lead in!
abstract: Targeted α-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissue than β-emitters because of the combination of short path length (50-80 μm) with the high linear energy transfer (100 keV μm(-1)) of this emission. These physical properties offer the real possibility of targeted (pre-targeted) α-therapy suitable for the elimination of minimal residual or micrometastatic disease. Targeted and pre-targeted radioimmunotherapy (RIT) using α-emitters such as (212)Bi (T(1/2) = 1.01 h) and (212)Pb (T(1/2) = 10.6 h) has demonstrated significant utility in both in vitro and in vivo model systems. (212)Pb, a promising α-particle emitting source, is the longer-lived parent nuclide of (212)Bi, and serves as an in vivo generator of (212)Bi. The radionuclide has been successfully used in RIT and pre-targeted RIT and demonstrated an enhanced therapeutic efficacy in combination with chemotherapeutics, such as gemcitabine and paclitaxel. The following perspective addresses the modes of radionuclide production, radiolabelling and chelation chemistry, as well as the application of (212)Pb to targeted and pre-targeted radiation therapy.
authors.affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, NIH, Building 10, Room 1B40, 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
authors.forename: Kwon
authors.initials: K
authors.lastname: Yong
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D056831:Coordination Complexes / Q000737:chemistry / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007854:Lead / Q000737:chemistry / Q000627:therapeutic use*; D007856:Lead Radioisotopes / Q000737:chemistry; D018499:Linear Energy Transfer; D009369:Neoplasms / Q000532:radiotherapy; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D007856:Lead Radioisotopes; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D007854:Lead